Exploration of the chemical and physical factors involved in stabilization of glucose oxidase based polarographic glucose sensors has made possible the development of a design capable of giving reliable continuous quantitative glucose signals over a long period of time. We have found a way to make this enzyme electrode essentially independent of oxygen tension within the ranges encountered in various implant sites. The sensor functions well in body fluids and even in whole blood. The sensor can be sterilized and can be stored for months. When the present glucose sensor is removed after implantation in the rat peritoneum for six months it is found to be as active as when tested in vitro before implantation. This remarkable finding, together with other advances in sensor design, is the foundation for the present research. We plan to explore a large number of means of applying this knowledge, together with new knowledge, in the development of a number of glucose sensor designs. Implantable polarographic sensors are being designed and implanted together with various means of transporting the glucose signal outside the body. Radiotelemetry is already being used in the rat. The glucose sensor, together with potentiostatic and cyclic voltammetric circuits, will be implanted in a number of sites in normal and streptozotocin-induced diabetic rats. The best instrumental designs will be implanted in cats for detailed long-term studies. The implanted sensor's glucose signal will be compared with repeated (thousands of) measurements of blood glucose. In a later phase of this research one glucose sensor will be used to control an implanted insulin pump while another glucose sensor will be used to continuously transmit the blood glucose signal from the animal to a receiver and recorder. In the last phase, the signal from the glucose sensor implanted in a diabetic animal will be used to operate an insulin infusion pump.